The aim of the Misteli laboratory is to understand how genomes are organized in vivo and how the architectural organization of the genome contributes to its function in health and disease. To this end, we are employing cell biological and biochemical methods and we are developing advanced imaging methods to probe genome organization in living cells and tissues. In particular, we are taking advantage of high-throughput imaging approaches to map genome regions with high precision in a large number of samples allowing for systematic spatial mapping and implementation of screening approaches for discovery. We have also developed novel software tools to analyze spatial genome positioning and we have applied it to the analysis of genome organization differences in normal and cancer cells. Finally, we are exploring the molecular mechanisms of human aging and the relationship between aging and cancer. We use the rare premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) as a model system in these studies.